Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

Quality variation and salt-alkali-tolerance mechanism of Cynomorium songaricum: Interacting from microbiome-transcriptome-metabolome.

Addressing soil salinization and implementing sustainable practices for cultivating cash crops on saline-alkali land is a prominent global challenge. Cynomorium songaricum is an important salt-alkali tolerant medicinal plant capable of adapting to saline-alkali environments. In this study, two typical ecotypes of C. songaricum from the desert-steppe (DS) and saline-alkali land (SAL) habitats were selected. Through the integration of multi-omics with machine learning, the rhizosphere microbial communities, genetic maps, and metabolic profiles of two ecotypes were created and the crucial factors for the adaptation of C. songaricum to saline-alkali stress were identified, including 7 keystone OTUs (i.e. Novosphingobium sp., Sinorhizobium meliloti, and Glycomyces sp.), 5 core genes (cell wall-related genes), and 10 most important metabolites (i.e. cucurbitacin D and 3-Hydroxybutyrate) were identified. Our results indicated that under saline-alkali environments, the microbial competition might become more intense, and the microbial community network had the simple but stable structure, accompanied by the changes in the gene expression related to cell wall for adaptation. However, this regulation led to the reduction in active ingredients, such as the accumulation of flavonoids and organic acid, and enhanced the synthesis of bitter substances (cucurbitacin D), resulting in the decrease in the quality of C. songaricum. Therefore, compared to the SAL ecotype, the DS was more suitable for the subsequent development of medicinal and edible products of C. songaricum. Furthermore, to explore the reasons for this quality variation, we constructed a comprehensive microbial-genetic-metabolic regulatory network, revealing that the metabolism of C. songaricum was primarily influenced by genetic factors. These findings not only offer new insights for future research into plant salt-alkali tolerance strategies but also provide a crucial understanding for cultivating high-quality medicinal plants.

Clinical Effect of Vitamin E Combined with Recombinant Human Epidermal Growth Factor on the Recurrent Oral Ulcer and Effects of Serum Superoxide Dismutase, IL-10, and TNF-α.

Objective: To examine the therapeutic effects of vitamin E combined with recombinant human epidermal growth factor on recurrent oral ulcers as well as on the levels of serum superoxide dismutase (SOD), interleukin-10 (IL-10), and tumor necrosis factor- (TNF-α), to provide evidence to facilitate medical management. Method: From June 2021 to May 2022, 84 patients with recurrent oral ulcers assessed and treated in our hospital were assigned to the control group and observation group with 42 cases in each group. Vitamin E was administered to the control group, while recombinant human epidermal growth factor and vitamin E were administered to the observation group. The clinical efficacy, serum SOD level, inflammatory factor level (IL-10, TNF-α), immune function index, clinical symptom improvement, pain disappearance time, healing time of ulcer surface, and adverse reactions were examined. Results: Clinical efficacy of the observation group (92.86%) was considerably greater than the control group (73.81%), (P < .05). Following treatment, the observation group had comparatively higher levels of serum SOD and significantly decreased TNF-α and IL-10 concentrations compared to the control group (P < .05). Similarly, post-treatment, the observation group had substantially higher CD3+, CD4+, and CD4+/CD8+ concentrations and lower CD8+ concentrations compared to the normal control (P < .05). In contrast to the control group, the observation group's pain degree score, ulcer diameter, duration for pain relief, and ulcer surface healing time duration were reduced substantially (P < .05). Notably, the incidence of adverse reactions was fairly similar in both groups (P > .05). Conclusion: Vitamin E combined with recombinant human epidermal growth factor has a significant clinical effect on recurrent oral ulcers, can achieve rapid improvement of symptoms in patients, and is relatively safe to be used as a clinical therapy.

Geographical distribution-based differentiation of cultivated Angelica dahurica, exploring the relationship between the secretory tract and the quality.

Based on geographical distribution, cultivated Chinese Angelica dahurica has been divided into Angelica dahurica cv. 'Hangbaizhi' (HBZ) and Angelica dahurica cv. 'Qibaizhi' (QBZ). Long-term geographical isolation has led to significant quality differences between them. The secretory structure in medicinal plants, as a place for accumulating effective constituents and information transmission to the environment, links the environment with the quality of medicinal materials. However, the secretory tract differences between HBZ and QBZ has not been revealed. This study aimed to explore the relationship between the secretory tract and the quality of two kinds of A. dahurica. Root samples were collected at seven development phases. High-Performance Liquid Chromatography (HPLC) and Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI-MSI) were used for the content determination and spatial location of coumarins. Paraffin section was used to observe and localize the root secretory tract. Origin, CaseViewer, and HDI software were used for data analysis and image processing. The results showed that compared to QBZ, HBZ, with better quality, has a larger area of root secretory tracts. Hence, the root secretory tract can be included in the quality evaluation indicators of A. dahurica. Additionally, DESI-MSI technology was used for the first time to elucidate the temporal and spatial distribution of coumarin components in A. dahurica root tissues. This study provides a theoretical basis for the quality evaluation and breeding of improved varieties of A. dahurica and references the DESI-MSI technology used to analyze the metabolic differences of various compounds, including coumarin and volatile oil, in different tissue parts of A. dahurica.

[Effect of Bushen Chushi() decoction combined with platelet-rich plasma on regulating TGF-ß1 and Smad-1 expression in serum of knee osteoarthritis patient].

OBJECTIVE: To investigate the effect of Bushen Chushi decoction combined with platelet-rich plasma(PRP) to treat knee osteoarthritis(KOA) in early and middle stage and its regulation on TGF-ß1 and Smad-1 expression in serum. METHODS: Total of 45 patients with KOA in early and middle stage from May 2020 to April 2022 were treated and divided into control group and observation group. In control group, there were 30 patients including 12 males and 18 females, aged from 43 to 69 years old with an average of(57.3±6.5) years old and disease duration ranged from 1.5 to 5.0 years with an average of(3.8±1.7) years, and there were 8 cases in gradeⅠ, 13 cases in gradeⅡ, and 9 cases in grade Ⅲ according to Kellgren-Lawrence Grade, PRP 5 ml was injected into knee joint on the first day of No1, 3 week together for 2 times. In the observation group, there were 15 cases including 7 males and 8 females, aged from 45 to 70 years old with an average of (56.7±6.2) years old and disease duration ranged from 1.8 to 5.7 years with an average of (4.0±1.8) years, there were 4 cases in gradeⅠ, 9 cases in gradeⅡand 4 cases in grade Ⅲ according to the Kellgren-Lawrence Grade, PRP 5 ml were injected into knee joints that the time and frequency were the same as those in the control group, and at the same time Bushen Chushi decoction orally were taken 1 dose per day with a total of 28 doses. All patients were treated for four weeks. Visual analogue scale(VAS) and Lequesne MG score before and after treatment were used to evaluate improvement of knee pain and joint function. The TGF-ß1 and Smad-1 levels in serum were measured before and after treatment in two groups. The incidence of complications in two groups was observed. RESULTS: All patients were followed up for 26 to 30 days with an average of (28.0±0.6) days. There was no significant difference in VAS and knee Lequesne MG scores between two groups before treatment(P>0.05). The scores of VAS and knee Lequesne MG on the first day after treatment in both groups were lower than those before treatment(P<0.05). The VAS and knee Lequesne MG scores in observation group were lower than those in control group(P<0.05) on the first day after treatment. The TGF-ß1 level in serum after treatment were higher significantly than that before treatment in two groups(P<0.05). After treatment, TGF-ß1 level in serum in observation group were lower than those in control group with statistically significant differences(P<0.05). The Smad-1 levels in serum after treatment in observation group were higher significantly than that in control group(P<0.05). The levels of Smad-1 were not statistically significant between before and after treatment(P>0.05). There was no significant difference in postopertaive complications between two groups (P>0.05). CONCLUSION: The efficacy of Bushen Chushi decoction combined with PRP in treatment of early and middle KOA is better than that of PRP injection alone. The combined treatment could reduce TGF-ß1 level and increase Smad-1 level in serum, which may be a mechanism to inhibit inflammation and alleviate cartilage degeneration to some extent.

Ameliorating parkinsonian motor dysfunction by targeting histamine receptors in entopeduncular nucleus-thalamus circuitry.

In Parkinson's disease (PD), reduced dopamine levels in the basal ganglia have been associated with altered neuronal firing and motor dysfunction. It remains unclear whether the altered firing rate or pattern of basal ganglia neurons leads to parkinsonism-associated motor dysfunction. In the present study, we show that increased histaminergic innervation of the entopeduncular nucleus (EPN) in the mouse model of PD leads to activation of EPN parvalbumin (PV) neurons projecting to the thalamic motor nucleus via hyperpolarization-activated cyclic nucleotide-gated (HCN) channels coupled to postsynaptic H2R. Simultaneously, this effect is negatively regulated by presynaptic H3R activation in subthalamic nucleus (STN) glutamatergic neurons projecting to the EPN. Notably, the activation of both types of receptors ameliorates parkinsonism-associated motor dysfunction. Pharmacological activation of H2R or genetic upregulation of HCN2 in EPNPV neurons, which reduce neuronal burst firing, ameliorates parkinsonism-associated motor dysfunction independent of changes in the neuronal firing rate. In addition, optogenetic inhibition of EPNPV neurons and pharmacological activation or genetic upregulation of H3R in EPN-projecting STNGlu neurons ameliorate parkinsonism-associated motor dysfunction by reducing the firing rate rather than altering the firing pattern of EPNPV neurons. Thus, although a reduced firing rate and more regular firing pattern of EPNPV neurons correlate with amelioration in parkinsonism-associated motor dysfunction, the firing pattern appears to be more critical in this context. These results also confirm that targeting H2R and its downstream HCN2 channel in EPNPV neurons and H3R in EPN-projecting STNGlu neurons may represent potential therapeutic strategies for the clinical treatment of parkinsonism-associated motor dysfunction.

Metabolomics analysis reveals metabolite changes during freeze-drying and oven-drying of Angelica dahurica.

Angelica dahurica (Angelica dahurica Fisch. ex Hoffm.) is widely used as a traditional Chinese medicine and the secondary metabolites have significant pharmacological activities. Drying has been shown to be a key factor affecting the coumarin content of Angelica dahurica. However, the underlying mechanism of metabolism is unclear. This study sought to determine the key differential metabolites and metabolic pathways related to this phenomenon. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) based targeted metabolomics analysis was performed on Angelica dahurica that were freeze-drying (- 80 °C/9 h) and oven-drying (60 °C/10 h). Furthermore, the common metabolic pathways of paired comparison groups were performed based on KEEG enrichment analysis. The results showed that 193 metabolites were identified as key differential metabolites, most of which were upregulated under oven drying. It also displayed that many significant contents of PAL pathways were changed. This study revealed the large-scale recombination events of metabolites in Angelica dahurica. First, we identified additional active secondary metabolites apart from coumarins, and volatile oil were significantly accumulated in Angelica dahurica. We further explored the specific metabolite changes and mechanism of the phenomenon of coumarin upregulation caused by temperature rise. These results provide a theoretical reference for future research on the composition and processing method of Angelica dahurica.

Research on Mechanisms of Chinese Medicines in Prevention and Treatment of Postoperative Adhesion.

Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.

Electroacupuncture Alleviates Pain Responses and Inflammation in Collagen-Induced Arthritis Rats via Suppressing the TLR2/4-MyD88-NF-κB Signaling Pathway.

Results: EA intervention and OxPAPC injection could relieve mechanical allodynia and thermal hyperalgesia caused by CIA. Paw edema and pathological damage of synovium were significantly ameliorated after EA intervention and OxPAPC injection. Furthermore, EA intervention and OxPAPC injection markedly reduced the contents of serum TNF-α, IL-1ß, and IL-6, as well as the protein expression levels of synovial TLR2, TLR4, MyD88, and NF-κB p-p65. In particular, the expression of TLR2 and TLR4 on synovial fibroblasts and macrophages in synovium was significantly reduced by EA intervention. Conclusions: Repeated EA stimulation at ST36 and SP6 can effectively relieve joint pain and synovial inflammation caused by RA in CIA rats. The analgesic and anti-inflammatory effect of EA may be closely related to the inhibition of innate immune responses driven by the TLR2/4-MyD88-NF-κB signaling pathway in the synovium.

["Component-target-efficacy" network analysis and experimental verification of Qingkailing Oral Preparation].

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.

Oyster culture changed the phosphorus speciation in sediments through biodeposition.

Phosphorus speciation in the sediments is regulated by a series of physicochemical and microbial processes, and directly affects water phosphorus pool. However, the influence of culture activities and microbial metabolism on the sedimentary phosphorus speciation is poorly studied. In this study, we compared the abundance of distinguishable phosphorus phases and other physicochemical properties of sediments from oyster-farming areas and reference areas. The Geochip 5.0 technique was introduced to reveal the microbiological mechanisms of phosphorus metabolic alteration. The results showed that oyster culture enhanced the bioavailability of phosphorus in sediments. The free organic phosphorus was reduced significantly, whereas the free inorganic phosphorus and iron-bound phosphorus greatly increased in the oyster culture area (P ≤ 0.05). Moreover, the results of Geochip showed that the oyster culture reshaped the microbial network structure in sediments, with typical phosphate-solubilizing and phosphorus-accumulating microbes being enriched by 17.76% and 10.60%. The abundance of functional genes related to the main phosphorus cycle pathways were also significantly increased (P ≤ 0.05) in the culture area compared to the reference area. This work suggested that oyster culture can greatly improve the microbial phosphorus metabolism and provided insights into the environmental recovery and reconstruction from marine aquaculture activities.

Traditional Chinese Medicine Against Gouty Arthritis via Regulating Inflammatory Signaling Pathway： A Review / 中国实验方剂学杂志

Gouty arthritis （GA） is a metabolic disease caused by disorders of purine metabolism and/or abnormal excretion of uric acid in the body. Its pathogenesis is mostly related to dietary structure as well as excessive intake of protein， sugar and fat， and the clinical manifestations are joint redness， swelling， heat and pain， which seriously affect the daily life of patients. Therefore， it is urgent to carry out research on anti-GA drugs. Western drugs for the treatment of GA， such as colchicine， can relieve pain in the short term， but with obvious side effects in long-term treatment. Traditional Chinese medicine has definite efficacy and high safety in the treatment of GA and is more acceptable to patients than western medicine. Modern medical research has concluded that inflammatory factors， oxidative stress， apoptosis and intestinal dysbacteriosis are closely related to the pathogenesis of GA. In-depth research has found that single traditional Chinese medicine and its compounds can regulate Toll-like receptors/myeloid differentiation factor 88 （TLRs/MyD88） signaling pathway， NLR family pyrin domain containing 3 （NLRP3） inflammasome， nuclear transcription factor-κB （NF-κB） and other inflammatory signaling pathways， and further intervene in the downstream cytokines such as interleukin-1β （IL-1β）， interleukin-2 （IL-2）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， peroxisome proliferator-activated receptor γ （PPARγ）， nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-α（IκB-α） and aspartate-specific cysteine protease 1 （Caspase-1） to reduce inflammatory factors and increase anti-inflammatory factors， thereby exerting the anti-GA role. Therefore， this paper summarized and elaborated the experiments of inflammatory response mediated by traditional Chinese medicines and their compounds via regulating inflammatory signaling pathways in recent years， which provides new ideas and theoretical basis for finding more related anti-inflammatory traditional Chinese medicines for the treatment of GA.

"Component-target-efficacy" network analysis and experimental verification of Qingkailing Oral Preparation / 中国中药杂志

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.

Research on Mechanisms of Chinese Medicines in Prevention and Treatment of Postoperative Adhesion / 中国结合医学杂志

Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.

Evidence construction of baicalin for treating myocardial ischemia diseases: A preclinical meta-analysis.

BACKGROUND: Baicalin, a flavonoid glycoside isolated from Scutellaria baicalensis Georgi, has shown potential pharmacological effects on myocardial ischemia diseases. Nevertheless, systematic preclinical studies on baicalin in the treatment of ischemic diseases are scarce. PURPOSE: To assess the efficacy and potential mechanisms of baicalin in myocardial ischemia (RI), myocardial ischemia-reperfusion (IR) injury and myocardial infarction (MI) animal models for future clinical research. METHODS: Preclinical studies published prior to August 27th, 2022 were retrieved from PubMed, Embase, Web of Science and Cochrane Library. CAMARADES list was used to evaluate the quality of included researches. Meta-analyses of cardiac pathology and function parameters, myocardial injury markers and other indicators were performed by STATA 15.0 software. Potential mechanisms are categorized and summarized. Dose-response interval analyses were used to analyze the dose-response relationship between baicalin and myocardial ischemia disease. RESULTS: Fourteen studies and 222 animals were included in the analysis. The results showed that compared with the control group, baicalin could reduce myocardial infarction size associated with cardiac pathological condition and the corresponding cardiac pathological index containing CK-MB, CK and cTnT. Additionally, heart function indicators including LVSP, LVFS, LVEF, -dp/dt max, dp/dt max were increased by baicalin. As for subgroup analyses, baicalin also demonstrated certain effect on CK-MB and LVSP by administration method or stage. Furthermore, it displayed obvious effect on myocardial ischemia diseases when the dose is maintained at 100-150 mg/kg based on dosage analyses. CONCLUSION: Based on the relevant literature retrieved, this is the first meta-analysis on baicalin in treating myocardial ischemia diseases. Notably, we linked the dynamic development of the disease and discussed it pertinently, from RI, IR injury to MI. Baicalin exhibits positive effects on myocardial ischemia diseases (especially when the dose is 100-150 mg/kg), which is achieved by regulating key pathological indicators and various signaling pathways.

Disturbance of Fatty Acid Metabolism Promoted Vascular Endothelial Cell Senescence via Acetyl-CoA-Induced Protein Acetylation Modification.

Endothelial cell senescence is the main risk factor contributing to vascular dysfunction and the progression of aging-related cardiovascular diseases. However, the relationship between endothelial cell metabolism and endothelial senescence remains unclear. The present study provides novel insight into fatty acid metabolism in the regulation of endothelial senescence. In the replicative senescence model and H2O2-induced premature senescence model of primary cultured human umbilical vein endothelial cells (HUVECs), fatty acid oxidation (FAO) was suppressed and fatty acid profile was disturbed, accompanied by downregulation of proteins associated with fatty acid uptake and mitochondrial entry, in particular the FAO rate-limiting enzyme carnitine palmitoyl transferase 1A (CPT1A). Impairment of fatty acid metabolism by silencing CPT1A or CPT1A inhibitor etomoxir facilitated the development of endothelial senescence, as implied by the increase of p53, p21, and senescence-associated ß-galactosidase, as well as the decrease of EdU-positive proliferating cells. In the contrary, rescue of FAO by overexpression of CPT1A or supplement of short chain fatty acids (SCFAs) acetate and propionate ameliorated endothelial senescence. In vivo, treatment of acetate for 4 weeks lowered the blood pressure and alleviated the senescence-related phenotypes in aortas of Ang II-infused mice. Mechanistically, fatty acid metabolism regulates endothelial senescence via acetyl-coenzyme A (acetyl-CoA), as implied by the observations that suppression of acetyl-CoA production using the inhibitor of ATP citrate lyase NDI-091143 accelerated senescence of HUVECs and that supplementation of acetyl-CoA prevented H2O2-induced endothelial senescence. Deficiency of acetyl-CoA resulted in alteration of acetylated protein profiles which are associated with cell metabolism and cell cycle. These findings thus suggest that improvement of fatty acid metabolism might ameliorate endothelial senescence-associated cardiovascular diseases.

Exploring the Protective Effect and Mechanism of Buddlejae Flos on Sodium Selenite-Induced Cataract in Rats by Network Pharmacology, Molecular Docking, and Experimental Validation.

Objective: Buddlejae Flos has a long history of utilization by humans to treat ophthalmic diseases. Although in vitro study revealed that it can be used for treating cataract, the bioactive components and the mechanism of efficacy remained unclear. This study aims to discover the bioactive components and mode of efficacy of Buddlejae Flos in cataract treatment. Methods: Several databases were screened for bioactive components and corresponding targets, as well as cataract-related targets. Using the String database, common targets were determined and utilized to construct protein-protein interactions (PPI). The drug-component-target-disease network map was drawn using Cytoscape software. R language was utilized to execute Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analysis. Molecular docking was done through Schrödinger Maestro software utilization. Luteolin's (LUT) effect on cataract induced by sodium selenite in rat pups was evaluated. Results: Six bioactive components with 38 common targets were identified as being associated with cataract. TP53, AKT1, EGFR, CASP3, TNF, ESR1, INS, IL6, HIF1A, and VEGFA were identified as core targets in PPI analysis, and the binding energy of LUT with AKT was the lowest. LUT has been demonstrated to significantly lower MDA levels, raise glutathione (GSH) levels, and boost the activity of antioxidant enzymes like GST, SOD, GPx, and CAT. After LUT treatment, TNF-a, IL-2, and IL-6 levels were significantly lowered. Bcl-2 mRNA expression levels and p-PI3K and p-AKT protein expression were significantly elevated. In contrast, caspase-3 and Bax mRNA expression levels were significantly decreased. Conclusion: This study demonstrates that LUT is a possible bioactive component that may be utilized for cataract treatment. Its mode of action includes oxidative stress suppression, reducing inflammation, and inhibiting apoptosis via regulating the PI3K/AKT single pathway.

A novel water-soluble flavonol-based fluorescent probe for highly specific and sensitive detection of Al3+ and its application in onion and zebrafish.

A novel and simple turn-on fluorescence probe (HD) for Al3+ detection was successfully developed based on flavonol derivatives. This probe exhibited a significantly enhanced fluorescence response toward Al3+ in aqueous solution which could be observed by naked-eye from poor fluorescence to strong light green emission. The probe HD displays highly specific detection for Al3+ over other competitive metal ions, and the detection limit of probe HD for Al3+ was determined to be 2.57 × 10-8 M, which are much lower than the World Health Organization (WHO) guideline value for drinking food/water. The binding stoichiometry of probe HD with Al3+ was determined to be 1:1 according to Job's plot and ESI-HRMS analysis, and the binding constant was calculated to be 2.01 × 104 M-1. The probe HD exhibited high selectivity, high sensitivity, good anti-interface ability, and wide pH application range as well as the quantitative determination in the detection of Al3+. The coordination mechanism of probe HD with Al3+ was supported by density functional theory (DFT) calculations and HRMS analysis. In addition, the probe HD was found to have good cell permeability and could be applied for live-cell imaging to detect Al3+ in onions and zebrafish.

[Identification of Q-markers for Cistanches Herba based on HPLC-Q-TOF-MS/MS and network pharmacology].

This study aims to establish a method for analyzing the chemical constituents in Cistanches Herba by high performance liquid chromatography(HPLC) and quadrupole-time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS), and to reveal the pharmacological mechanism based on network pharmacology for mining the quality markers(Q-markers) of Cistanches Herba. The chemical constituents of Cistanche deserticola and C. tubulosa were analyzed via HPLC-Q-TOF-MS/MS. The potential targets and pathways of Cistanches Herba were predicted via SwissTargetPrediction and DAVID. The compound-target-pathway-pharmacological action-efficacy network was constructed via Cytoscape. A total of 47 chemical constituents were identified, involving 95 targets and 56 signaling pathways. We preliminarily elucidated the pharmacological mechanisms of echinacoside, acteoside, isoacteoside, cistanoside F, 2'-acetylacteoside, cistanoside A, campneoside Ⅱ, salidroside, tubuloside B, 6-deoxycatalpol, 8-epi-loganic acid, ajugol, bartsioside, geniposidic acid, and pinoresinol 4-O-ß-D-glucopyranoside, and predicted them to be the Q-markers of Cistanches Herba. This study identified the chemical constituents of Cistanches Herba, explained the pharmacological mechanism of the traditional efficacy of Cistanches Herba based on network pharmacology, and introduced the core concept of Q-markers to improve the quality evaluation of Cistanches Herba.

[Effects of transcutaneous auricular vagus nerve stimulation on bone and cartilage destruction in rats with rheumatoid arthritis].

OBJECTIVE: To observe the alleviating effect of transcutaneous auricular vagus nerve stimulation (taVNS) on articular cartilage and bone destruction in rats with collagen-induced arthritis (CIA), and explore the cellular and molecular mechanisms of taVNS against rheumatoid arthritis (RA). METHODS: The male SD rats were randomly divided into normal control group (n=12), model group (n=12), and taVNS group (n=12). The CIA rat model was established by multi-point injection of emulsion prepared from type Ⅱ bovine collagen and Freund's incomplete adjuvant into the root of rat tail. The rats in the taVNS group were treated with taVNS at bilateral auricular conchae, 30 min per time, once a day, for consecutive 28 d. The cartilage destruction of the ankle joint was observed by safranin O-fast green staining, the production of osteoclasts in the joint tissue by tartrate-resistant acid phosphatase (TRAP) staining, and the bone erosion by X-ray and Micro-CT imaging. The protein expression levels of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, receptor activator of nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG) in the synovial tissues were detected by Western blot. RESULTS: Compared with the normal control group, the CIA rats presented with typical RA symptoms and elevated arthritis index (AI,P<0.05). After intervention with taVNS, the AI remarkably declined in comparison with that in the model group (P<0.05). Compared with the control group, the model group displayed loss of cartilage matrix in the ankle joint, thinned cartilage layer, obvious cartilage damage, and increased number of osteo-clasts in the joint (P<0.01); the imaging results showed bone loss and three-dimensional structural destruction of ankle joint and aggravated bone erosion (P<0.01); the expression levels of MMP-1, MMP-3 and MMP-13, and RANKL/OPG ratio were significantly elevated in the synovial tissue of ankle joint (P<0.01, P<0.05), while the expression level of OPG was decreased (P<0.05). Compared with the model group, taVNS resulted in relatively intact cartilage layer of ankle joint, alleviated cartilage destruction, decreased number of osteoclasts (P<0.01), improved bone erosion, loss, and three-dimensional structural destruction (P<0.01), and diminished MMP-1, MMP-3, and MMP-13 expression and RANKL/OPG ratio in the synovial tissue of ankle joint (P<0.05, P<0.01), while the expression level of OPG was increased (P<0.05). CONCLUSION: taVNS effectively relieves bone and cartilage destruction in CIA rats, which might be related to its efficacy in reducing the production of osteoclasts in joint tissues and down-regulating the expression levels of MMP-1, MMP-3 and MMP-13, and RANKL/OPG ratio.